Measles Virus Fusion Protein Presented in an Immune-stimulating Complex (Iscom) Induces Haemolysis-inhibiting and Fusion-inhibiting Antibodies, Virus-specific T Cells and Protection in Mice

Abstract

SUMMARYImmune-stimulating complexes (iscoms), which have recently been shown to be highly effective for the antigenic presentation of membrane proteins of viruses, were prepared with affinity-purified fusion (F) protein of measles virus (MV), using an adaptation of the standard method for iscom preparation. Immunization of monkeys with the F iscom preparation induced biologically active anti-F protein antibodies as was shown in haemolysis inhibition and cell-cell fusion inhibition tests. A whole MV iscom preparation, which also contained the haemagglutinin protein, induced not only haemolysis-inhibiting antibodies, but, in contrast to the F iscom preparation, also haemagglutination-inhibiting and virus-neutralizing antibodies. In addition the F iscom preparation was shown to activate measles virus-specific T cells in mice. This was demonstrated by the generation of an MV-specific delayed type hypersensitivity response in F iscom-immunized animals and by the isolation of T cell clones specific for MV F protein with the T helper phenotype. Vaccination of mice with MV iscom or F iscom protected them from MV-induced fatal encephalopathy. The data concerning the immunogenicity of MV proteins presented in iscoms are discussed in relation to their potential for the development of an inactivated measles vaccine.

The iscom structure as an immune-enhancing moiety: experience with viral systems

“…Iscoms containing immuno-affinity-purified F (F-iscom) induced antibodies with haemolysis inhibition (HLI) activity but devoid of VN activity. Both F and H iscom preparations induced protection against intracerebral challenge with a rodent-adapted measles virus strain (De Vries et al, 1988a ;Varsanyi et al, 1987). Immunization with F-iscom induced a measles-virus-specific cellular response, delayed type hypersensitivity (DTH) and measles-virus-specific T-cell clones could be generated from these mice (De Vries et al, 1988a).…”

“…Both F and H iscom preparations induced protection against intracerebral challenge with a rodent-adapted measles virus strain (De Vries et al, 1988a ;Varsanyi et al, 1987). Immunization with F-iscom induced a measles-virus-specific cellular response, delayed type hypersensitivity (DTH) and measles-virus-specific T-cell clones could be generated from these mice (De Vries et al, 1988a). MV iscom also induced humoral (in monkey) and cellular (in mice) immune responses in the presence of passively transferred antibodies, a situation that mimics vaccination in the presence of maternal antibodies (De Vries et al, 1990).…”

“…Quil A is a necessary constituent of the iscom structure. The size and morAntigen nature Name Mowatt et al, 1991a/b Lovgren et al, 1987Erturk et al, 1989Trudel et al, 1987, 1988Wahren et al, 1987Tsuda et al, 1991Morgan et al, 1988Howard et al, 1987Trudel et al, 1988Carlson et al, 1991De Vries et al, 1988aDe Vries et al, 1988bVisser et al, 1989Trudel et al, 1989Trudel et al, 1992Fedaku et al, 1992Jones et al, 1988Merza et al, 1991Osterhaus et al, 1992Takehashi et al, 1990Pyle et al, 1989Nagy et al, 1990Winter et al, 1988…”

The PorB porin from commensal Neisseria lactamica induces Th1 and Th2 immune responses to ovalbumin in mice and is a potential immune adjuvant

“…We propose that the PorB porin from commensal N. Lactamica acts as an immune adjuvant and has the potential of being developed as a potent immune modulator derived from a non-pathogenic bacterium, which would positively affect ease of manufacturing. Examples of adjuvants are oil emulsions [4][5][6], squalene (MF59) [7], immune stimulating complexes (ISCOMs [8,9]) with Quil-A and both gram-negative bacteria and bacterial products [4,[10][11][12]. These include DNA with immunostimulatory CpG motifs (one of the most powerful adjuvants [13]), Bordetella pertussis toxin [2,14], Corynebacterium granulosum derived P40 component [15], MPL [16], Mycobacterium and its components (Freund adjuvant) [4,17], Cholera toxin [18] and porins from various organisms such as Fusobacterium nucleatum [19], Shigella [20][21][22], Salmonella [22,23] and Neisseria meningitidis and gonorrhoeae [24][25][26][27][28][29].…”

ISCOMs: an adjuvant with multiple functions

“…When ISCOMs are made, these molecules are extracted by detergent treatment and integrate into the lipid-saponin matrix when the detergent is removed and ISCOM particles form [13,16]. Regardless of the molecular weight, level of glycosylation, or tertiary structure of incorporated proteins, the ISCOMs that are generated are usually indistinguishable from Iscom Matrix when examined by electron microscopy [5,8,16,29,31] or their sedimentation rate in sucrose gradients [32]. The degree of incorporation is usually determined indirectly by the coincidence of the selected protein and ISCOM particles in the same sucrose density gradient fraction [29,31].…”